Many pharmaceutical compounds approved for the treatment of a myriad of diseases and disorders include a carboxylic acid residue. The carboxylic acid functional group is oftentimes directly involved in binding with the biological target, resulting in a beneficial therapeutic effect of the compound. Occasionally, however, the carboxylic acid is also associated with an undesirable pharmacokinetic profile. Such undesirable characteristics may include limited permeability, toxicity, and metabolic instability.
One example of a carboxylic acid-containing pharmaceutical compound is compound 12:
While compound 12 shows promise as a treatment for Alzheimer's disease, the carboxylic acid moiety impedes the compound's ability to most effectively cross the blood brain barrier. An inability to cross the blood brain barrier inhibits a compound's ability to act on targets within the brain.
As such, bioisosteric replacements for the carboxylic moiety, that is, moieties that mimic the function of the carboxylic acid group but that result in, for example, improved pharmacokinetic, toxicological, and/or safety profiles, especially of compound 12, are needed.